Table 5.

Biologic Immune Response Modulators Targeting Lymphocytes

Immune Response Modulator	Agent(s)	Target Cell	Mechanism(s)	Immunologic Effects	Reported Infectious Complications	Treatment Indications
Anti-thymocyte globulin	ATG: Thymoglobulin (rabbit) Atgam (equine)	T lymphocyte	Polyclonal immunoglobulin against human T cell markers T cell depletion by cell death Disruption of T cell APC interaction	Depletion of circulating lymphocytes Alters function of T cells involved in humoral and in cell-mediated immunity	Herpes virus infections, particularly CMV	Organ transplant rejection Graft versus host disease prophylaxis Aplastic anemia
Monoclonal antibodies to T cells	OKT3	T lymphocyte	Binds to TCR-CD3 complex on T cells and blocks T cell proliferation and function	Profound T cell lymphopenia and poor function	Herpesviruses (HSV CMV EBV-associated LPD*) Pneumocystis jirovecii Listeria Mycobacteria Nocardia Toxoplasmosis	Acute organ transplant rejection
	Basiliximab	T lymphocyte	Binds to IL-2 receptor alpha chain (CD25), inhibiting lymphocyte activation	Impairment of antigen-specific cytotoxic T cell response	Incidence of infections not increased when added to dual immunosuppression regimens (steroids/cyclosporine)	Organ transplant rejection Graft versus host disease
Monoclonal antibody to B cells	Rituximab Ofatumumab	B cell from pre-B cell to pre-plasma cell stage	B cell death by complement-, cell mediated-, and antibody- dependent cellular cytotoxicity	Peripheral B cell depletion for 6–9 months or longer Hypogammaglobulinemia	Hepatitis B virus Hepatitis C virus JC virus (PML**) Herpesviruses (HSV, VZV, CMV) Parvovirus B19 West Nile virus Enteroviral encephalitis If hypogammaglobulinemia severe: Viral and bacterial sinusitis and pneumonia	B cell non-Hodgkin’s lymphoma CLL Autoimmune disorders: RA, Wegener’s granulomatosis, microscopic polyangiitis
	Belimumab	B lymphocytes	Inhibits the binding of soluble human B lymphocyte stimulator protein (BLyS) to its receptors on B cells	Inhibits the survival of B cells Reduces differentiation of B cells into immunoglobulin-producing plasma cells	Cellulitis Pneumonia JC virus (PML) CMV pneumonia Coccidiodomycosis	Systemic lupus erythematosus
Monoclonal antibody to T and B cells	Alemtuzumab (Campath and Lemtrada)	T and B lymphocytes, plus monocytes, macrophages, and natural killer cells	Antibody-dependent and complement-mediated cell lysis after binding to CD52	Profound and prolonged depletion of T and B lymphocytes, natural killer cells, and monocytes	Bacterial sepsis, pneumonia Herpesviruses (HSV, CMV, VZV EBV-associated LPD*) Hepatitis B virus Hepatitis C virus Adenovirus JC virus PML IFI§: aspergillosis, mucormycosis, histoplasmosis, cryptococcosis, pneumocystosis Nocardia Mycobacteria Toxoplasmosis	Campath-B cell chronic lymphocytic leukemia Lemtrada-relapsing, remitting multiple sclerosis
Fusion proteins disrupting T cell costimulation	Abatacept	T lymphocyte	Binds to CD80 and CD86 antigen presenting cells	Suppresses T cell activation	Bacterial pneumonia, Cellulitis, urinary tract infection	Refractory rheumatoid arthritis Juvenile idiopathic arthritis

^*LPD, lymphoproliferative disease;

^**PML, progressive multifocal leukoencephalopathy,

^§IFI: invasive fungal infection