But What About the T cells?

Let’s start with a few vocabulary words.

Those glory-seeking B cells get all the ink by quickly identifying and destroying the virus. But T cells, whose response appears somewhat latter, can destroy cells already infected, and unlike their B cell comrades, they hand around longer. T cells are lymphocytes, a type of white blood cell that is important in our long-term immunity. All T cells have a T-cell receptor on their surface that separates them from other lymphocytes.

• Memory T cells  - carry some of the long-term immune memory. When exposed to a familiar antigen that can rapidly produce two effector cells, T helpers and killers.
• CD4 T helper cells – their name comes from the glycoprotein (a sugar combined with a protein) found on their surface, CD4 – they have a Paul Revere like role, signaling other cells in the immunologic armamentarium.
• CD8 killer cells - have a different surface glycoprotein, CD8, which helps bind foreign antigens more tightly to these cytotoxic cells; they are especially useful in viral infections
• Both effector cells are capable of additional signaling to recruit other immune cells, using an old friend, cytokines.

Differentiating the types of T cells is costly and time-consuming, so much of the studies on our response to COVID-19 or the vaccines just report the total number of T cells. A new study characterizes the T cell response more thoroughly, confirming the immunologic response to vaccines and helping to understand what long-term immunity means and the cause of “breakthrough” infections.

The study looked at T cell populations in 11 individuals; all vaccinated, six with a breakthrough infection (none required hospitalization). Serologic measurements were made before vaccination and approximately two weeks after the first and then the second dose of both Moderna and Pfizer vaccines. Those infected had the “ancestral,” not the Delta variant of COVID-19. They also made use of convalescent plasma from patients who had recovered from their COVID-19 infections.

• In infection naïve patients, “the first vaccination dose primed a spike-specific CD4+ T cell response, which was further boosted with the second dose.” Convalescent plasma was “more disparate,” mounting a weaker response.
• The vaccine-induced T helper cells seemed to respond equally well to both the ancestral and beta variants
• “…spike-specific CD4+ T cells from convalescent individuals differ from those in infection-naïve individuals in that they appear to be more long-lived and may more readily migrate out of the blood to mucosal sites.” This can explain the apparent “weaker response.” The affinity for convalescent helper cells to gravitate to the nose and lungs may explain why repetitive infection is less frequent and severe – the immune cells are prepositioned to respond.

• The T killer cells' response was mutated in comparison to the boosts in helper cells.
• The populations of killer cells differed in those with vaccine and infection-mediated immune responses, although they were not as easily characterized as the changes in the helper cells.  

The researchers concluded that vaccines elicit a significant response by T cells and that variations in our response to COVID-19 variants are more likely due to differences in the vaccine’s impact on our acute immunologic response, the antibody creating B cells.

They found that two vaccine doses were necessary to achieve a sustained T cell response in infection-naïve individuals. [They did not look at the J&J vaccine, only the two mRNA vaccines]. But those individuals already surviving infection had a mixed response. Some had no alterations at all; others had both a boost in helper cells and a boost in helpers directed at areas of the virion beside the spike.

Finally, the immune response to COVID-19 infection compared to vaccination may also be longer-lasting because it seems to result in more memory cells. It also may be “more protective,” that is, fewer reinfections than breakthrough infections. The researchers believe this may be due to the increased affinity of the helper cells to the entryway of the virus, the nose, and lungs.

Source: mRNA vaccine-induced T cells respond identically to SARS-CoV-2 variants of concern but differ in longevity and homing properties depending on prior infection status eLife DOI: 10.7554/eLife.72619