CD4⁻CD8⁻ T cells control intracellular bacterial infections both in vitro and in vivo

Memory T cells, including the well-known CD4⁺ and CD8⁺ T cells, are central components of the acquired immune system and are the basis for successful vaccination. After infection, CD4⁺ and CD8⁺ T cells expand into effector cells, and then differentiate into long-lived memory cells. We show that a rare population of CD4⁻CD8⁻CD3⁺αβ⁺γδ⁻NK1.1⁻ T cells has similar functions. These cells potently and specifically inhibit the growth of the intracellular bacteria Mycobacterium tuberculosis (M. tb.) or Francisella tularensis Live Vaccine Strain (LVS) in macrophages in vitro, promote survival of mice infected with these organisms in vivo, and adoptively transfer immunity to F. tularensis LVS. Furthermore, these cells expand in the spleens of mice infected with M. tb. or F. tularensis LVS, and then acquire a memory cell phenotype. Thus, CD4⁻CD8⁻ T cells have a role in the control of intracellular infection and may contribute to successful vaccination.