Reference values established for virus specific T-cells in healthy adults

It remains unclear if there are lower levels of these antibodies in younger age groups.

The opportunistic viral infections that occur in people who are immunosuppressed, including those treated with either hematopoietic stem cell therapy or solid organ transplantation, can be lethal.  These infections can be treated by antivirals or, in recent years, by adoptive cell therapies using virus-specific T (VST) cells that have been primed to attack particular viruses ex vivo, and then infused into the patient. Indeed, a multi-virus, virus specific cytotoxic T-cell therapy Posoleucel (Viralym-M) is currently in phase III trials for transplant patients at risk for five common pathogens: HHV-6, EBV, CMV, BKV, JC virus and adenovirus. A phase II trial found a response rate of 93% (Tzannou 2017).

Such VST cells also occur naturally, as a part of the immune response to viruses that have reactivated from a state of latency. A team of investigators from Hannover Medical School in Germany reasoned that the circulating levels of such VST cells could help guide decisions about both prophylaxis and therapy of opportunistic infections. For example, if an opportunistic infection occurs in a patient with normal levels of circulating VST cells specific to that virus, it might make more sense to give antiviral therapy rather than adoptive T cell therapy (given that the patient already appeared to have sufficient numbers of virus-specific T cells). And adoptive therapy might make more sense if naturally-occurring VST cell numbers were low.

However, to interpret the meaning of such numbers of VST cells in immunosuppressed patients, the investigators decided that they needed to know what the numbers would be in a healthy normal control population.

The investigators developed an interferon-gamma enzyme-linked immunospot assay to measure the number of naturally occurring VST cells against these pathogens: HHV-6, EBV, CMV, HSV-1, HSV-2, VZV, adenovirus, BK virus, JC virus, respiratory syncytial virus, and influenza A virus.

This system then was used to measure the VST cell numbers in 151 healthy donors, 58% male, average age 42. Virtually all people who were seropositive to CMV, EBV or HHV-6 had VST cells that recognized at least one epitope of that virus.  For HHV-6, naturally-occurring VST cells directed at HHV-6 specifically against the U90 immediate early antigen were higher than those directed against U54 (92% of 561 subjects).

The next steps will be to use the same assay in people who are immunosuppressed, and to see the range of values for VSTs against these various viruses. Do the levels have prognostic value: for example, are people with naturally low levels of VSTs against a particular virus more likely to develop an opportunistic infection to that virus. Then, the clinical value of this assay can be assessed through controlled trials of both prophylaxis and treatment based on desired VST thresholds.

Read the full article: Schulze Lammers 2022