Abstract
Circulating, blood-borne SARS-CoV-2-reactive memory T cells in persons so far unexposed to SARS-CoV-2 or the vaccines have been described in 20-100% of the adult population. They are credited with determining the efficacy of the immune response in COVID-19. Here, we demonstrate the presence of preexisting memory CD4 + T cells reacting to peptides of the spike, membrane, or nucleocapsid proteins of SARS-CoV-2 in the bone marrow of all 17 persons investigated that had previously not been exposed to SARS-CoV-2 or one of the vaccines targeting it, with only 15 of these persons also having such cells detectable circulating in the blood. The preexisting SARS-CoV-2-reactive memory CD4 + T cells of the bone marrow are abundant and polyfunctional, with the phenotype of central memory T cells. They are tissue-resident, at least in those persons who do not have such cells in the blood, and about 30% of them express CD69. Bone marrow resident SARS-CoV-2-reactive memory CD4 + memory T cells are also abundant in vaccinated persons analyzed 10-168 days after 1°-4° vaccination. Apart from securing the bone marrow, preexisting cross-reactive memory CD4 + T cells may play an important role in shaping the systemic immune response to SARS-CoV-2 and the vaccines, and contribute essentially to the rapid establishment of long-lasting immunity provided by memory plasma cells, already upon primary infection.
Keywords: SARS-CoV-2; cross-reactive; human bone marrow; memory CD4+ T lymphocytes; peripheral blood; polyfunctional; tissue-resident memory T cells (Trm).
【저자키워드】 SARS-CoV-2, Peripheral blood, cross-reactive, tissue-resident memory T cells (Trm)., polyfunctional, memory CD4+ T lymphocytes, human bone marrow, 【초록키워드】 COVID-19, Efficacy, immune response, vaccination, Immunity, Vaccines, T cells, peptide, CD4, nucleocapsid protein, memory, Bone marrow, T cell, phenotype, membrane, memory T cell, Blood, Primary infection, Plasma cells, bone, CD69, systemic immune response, CD4+, circulating, Express, Cell, described, analyzed, investigated, detectable, provided, contribute, long-lasting, the vaccine, central memory, 【제목키워드】 memory, Bone marrow, individual, CD4+ T lymphocyte,