Acute T-cell Mediated Rejection of the Kidney: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC and Md Shahrier Amin, M.B.B.S., Ph.D.
July 20, 2026

Acute T-cell mediated rejection, also called acute cellular rejection, is a condition in which the immune system of a person who has received a kidney transplant attacks the transplanted kidney. It is driven by immune cells called T cells, which recognize the transplanted kidney as foreign, enter the tissue, and cause inflammation and injury. It is one of the most common forms of rejection, and when it is found early and treated, the kidney usually recovers.

The diagnosis is made from a biopsy of the transplanted kidney, and the report describes the findings using an international scoring system called the Banff classification. This article will help you understand the findings in your pathology report for acute T-cell mediated rejection, what each term means, and why it matters for your care. The section on the Banff classification explains the letters, numbers, and grades you are most likely to see on the report.

What causes acute T-cell mediated rejection?

Every cell in the body carries surface proteins called HLA antigens, which act like an identity badge that the immune system uses to tell “self” from “foreign.” A transplanted kidney comes from another person and carries different HLA antigens; despite careful matching, the recipient’s immune system can still recognize those antigens as foreign. In acute T-cell mediated rejection, T cells, a type of immune cell, respond by entering the transplanted kidney and attacking it directly. They damage the small tubes that process urine (tubules), the supporting tissue around them (the interstitium), and sometimes the blood vessels and filtering units. This kind of rejection can happen at any time after a transplant, from days to years later, and the risk is higher when immunosuppressant medication is reduced, missed, or not fully effective.

What are the symptoms of acute T-cell mediated rejection?

Many people with acute T-cell mediated rejection have no symptoms at all, and the problem is detected only through a rise in a blood test. Because the warning signs are often silent, people with a kidney transplant have regular blood tests to catch rejection early. When changes do occur, they may include:

A rise in the blood creatinine level, a waste product the kidney normally clears; this is usually the first sign, detected on routine bloodwork.
A drop in the amount of urine produced.
Swelling or tenderness over the transplanted kidney, which sits low in the abdomen.
Fluid retention and swelling of the legs, or a rise in blood pressure.
Protein in the urine.

Because a rising creatinine is often the only clue and appears without any feeling of illness, a biopsy is frequently performed simply to explain an unexpected change in the bloodwork.

How is the diagnosis made?

Acute T-cell mediated rejection is diagnosed from a biopsy of the transplanted kidney, in which a thin needle is used to take one or more small cores of tissue that a pathologist examines under the microscope. The biopsy is examined in several complementary ways, and each contributes something the report relies on.

Light microscopy, in which thin slices of tissue are stained and viewed under an ordinary microscope, is where the diagnosis is mainly made. The pathologist looks for two key changes: inflammation in the interstitium (the tissue between the tubules) and inflammation within the walls of the tubules themselves, called tubulitis. These are the features scored by the Banff system described below. A second technique, immunofluorescence, uses antibodies tagged with a glowing dye to detect specific proteins; in acute T-cell mediated rejection it is typically negative for a marker called C4d, which is important because a positive C4d points instead toward antibody-mediated rejection, a different process explained below. Electron microscopy, which magnifies tissue structures enormously, does not reveal anything specific to this type of rejection but helps rule out other conditions. A key part of the pathologist’s job is not only to confirm rejection but to determine which type it is, because the treatment differs.

The Banff classification

Transplant kidney biopsies worldwide are scored using the Banff classification, a system regularly updated by an international group of experts. It works by scoring individual features on a scale, then combining those scores into an overall grade. Seeing these letters and numbers on a report can be bewildering, so the pieces are explained here.

The individual scores

Two features are central to diagnosing acute T-cell mediated rejection, each scored from mild to severe:

Interstitial inflammation (the “i” score) — How much of the working kidney tissue is filled with inflammatory cells. i1 is 10 to 25% of the tissue, i2 is 26 to 50%, and i3 is more than 50%.
Tubulitis (the “t” score) — How many immune cells are found burrowing into the wall of each tubule. t1 is 1 to 4 cells per tubule, t2 is 5 to 10 cells, and t3 is more than 10 cells, or areas where the tubule is being destroyed.

A third feature becomes important when rejection involves the blood vessels:

Intimal arteritis (the “v” score) — Inflammation of the inner lining of the arteries, also called endothelialitis. v1 is mild to moderate inflammation of the artery lining, v2 is severe inflammation affecting a quarter or more of the vessel opening, and v3 is inflammation through the full thickness of the vessel wall, sometimes with vessel-wall death (fibrinoid necrosis). Vessel involvement is a sign of more serious rejection.

Borderline changes

Before the full grades, it is worth knowing about the borderline category, because it is one of the most common findings and may well be what your report says. Borderline (or “suspicious for”) acute T-cell mediated rejection means there is tubulitis with only limited interstitial inflammation, or interstitial inflammation with only mild tubulitis, not quite reaching the threshold for a full grade. It signals early or mild rejection that the transplant team weighs carefully, and it is often treated, though not always.

The grades of acute T-cell mediated rejection

When the thresholds are met, the rejection is assigned a grade. The grades fall into two groups: those confined to the tubules and interstitium (Grade I), and those that also involve the arteries (Grades II and III), which are more serious.

Grade IA — Significant interstitial inflammation (i2 or i3, more than a quarter of the tissue) together with moderate tubulitis (t2).
Grade IB — Significant interstitial inflammation (i2 or i3) together with severe tubulitis (t3).
Grade IIA — Mild to moderate inflammation of the artery lining (intimal arteritis, v1), with or without inflammation in the tubules and interstitium.
Grade IIB — Severe inflammation of the artery lining (v2), affecting a quarter or more of the vessel opening.
Grade III — Inflammation through the full thickness of the artery wall, or death of the vessel wall (fibrinoid necrosis), the most severe form.

In general, the higher the grade, the more intensive the treatment, and grades that involve the arteries (II and III) are treated more intensively than those confined to the tubules and interstitium. Your report may also carry other Banff scores that describe long-term changes or other processes; the ones above are the features specific to diagnosing and grading acute T-cell mediated rejection.

Other features described in the report

Alongside the Banff scores, the report often comments on additional findings that help complete the picture:

Tubular injury — Direct damage to the cells lining the tubules, which may appear swollen, flattened, or detached. It reflects how much immediate harm the rejection has done to the kidney’s working cells.
Microvascular inflammation — Inflammation in the smallest blood vessels (the capillaries). When prominent, this can be a clue that antibody-mediated rejection is also present, and it is one of the things that prompts closer attention to the C4d result.
Interstitial fibrosis and tubular atrophy — Scarring of the supporting tissue and shrinkage of the tubules. These reflect older, long-standing damage rather than the current rejection episode, and they help the team judge how much of the kidney is still healthy.
Glomerulosclerosis — Scarring of the glomeruli, the filtering units. It is described as global (the whole glomerulus) or segmental (only part), and a higher amount reflects more permanent injury.

Acute versus chronic rejection

Acute rejection develops over days to weeks and represents a sudden immune attack; when caught early, it usually responds well to treatment. Chronic rejection develops slowly over months to years and involves gradual scarring that is harder to reverse and tends to cause a slow decline in kidney function even with treatment. The distinction matters because the two are managed very differently, and the biopsy features, active inflammation versus established scarring, are what separate them.

T-cell mediated versus antibody-mediated rejection

There are two main ways the immune system can reject a transplanted kidney, and distinguishing between them is one of the most important jobs of the biopsy, because they are treated differently.

T-cell mediated rejection — The subject of this article. Immune cells called T cells enter the kidney and attack it directly, mainly injuring the tubules, the interstitium, and sometimes the arteries. The C4d marker is usually negative.
Antibody-mediated rejection — Driven not by cells but by antibodies, proteins made by a different arm of the immune system, that target the lining of the kidney’s blood vessels. It tends to injure the small vessels and is often marked by a positive C4d stain and by antibodies against the donor detectable in the blood.

Both types can occur at the same time, which is more serious and requires treating both. This is why a transplant biopsy report carefully addresses the C4d result and the blood vessel findings, not only the tubular inflammation.

What is the outlook?

The outlook for acute T-cell mediated rejection is generally good, especially when it is found early and confined to the tubules and interstitium (borderline or Grade I). Most of these episodes respond to treatment, and kidney function recovers. The outlook is more guarded when rejection involves the arteries (Grades II and III), when it does not respond to initial treatment, when it occurs alongside antibody-mediated rejection, or when the biopsy also shows extensive established scarring. Even a fully treated episode is important in the long term, because rejection episodes, particularly repeated or vascular ones, are among the factors that can shorten the lifespan of a transplanted kidney. This is the reason the transplant team treats rejection promptly and monitors closely afterward.

What happens after the diagnosis?

Acute T-cell mediated rejection is managed by the kidney transplant team, and treatment is guided by the Banff grade, the kidney function, and the person’s overall situation. The biopsy findings directly shape what the team considers. This is a general overview; the specific plan is individual, and this article does not recommend any particular treatment.

Corticosteroids — A short course of high-dose steroids given into a vein (pulse steroids) is the usual first treatment for borderline and Grade I rejection, and it resolves many episodes.
T-cell depleting therapy — For rejection that involves the arteries (Grade II or III), or that does not respond to steroids, a stronger treatment that removes T cells from the body, most often anti-thymocyte globulin (ATG), may be used.
Adjusting maintenance immunosuppression — Because rejection often indicates that the ongoing immunosuppressive medication was not fully effective, the transplant team usually reviews and adjusts these medications and looks into whether missed doses or drug levels played a role.
Follow-up — Kidney function is closely monitored after treatment, and a repeat biopsy is sometimes performed to confirm that the rejection has resolved, since kidney function alone does not always indicate whether inflammation has fully settled.

Throughout, the team balances enough immunosuppression to protect the kidney against the risks of too much, which include infection and, over time, certain cancers.

Questions to ask your doctor

What was the Banff grade of my rejection, and was it borderline or a full grade?
Did my rejection involve the blood vessels, or only the tubules and interstitium?
Was the C4d stain negative, and was antibody-mediated rejection ruled out?
Did the biopsy show any long-standing scarring, and how much healthy kidney remains?
What treatment do you recommend, and will it be steroids or a stronger therapy?
How quickly should my kidney function improve after treatment?
Will I need a repeat biopsy to confirm the rejection has resolved?
Do my immunosuppressant medications need to be changed?
Could missed doses or drug levels have contributed, and how can we prevent that?
Am I at higher risk of another rejection episode, or of chronic rejection?
What symptoms should prompt me to contact the transplant team?
How does this episode affect the long-term outlook for my transplant?